Guidelines for the Laboratory Diagnosis of Monkeypox in Korea.

While the coronavirus disease 2019 pandemic is ongoing, monkeypox has been rapidly spreading in non-endemic countries since May 2022. Accurate and rapid laboratory tests are essential for identifying and controlling monkeypox. Korean Society for Laboratory Medicine and the Korea Disease Prevention and Control Agency have proposed guidelines for diagnosing monkeypox in clinical laboratories in Korea. These guidelines cover the type of tests, selection of specimens, collection of specimens, diagnostic methods, interpretation of test results, and biosafety. Molecular tests are recommended as confirmatory tests. Skin lesion specimens are recommended for testing in the symptomatic stage, and the collection of both blood and oropharyngeal swabs is recommended in the presymptomatic or prodromal stage.

Guidelines for Mobile Laboratories for Molecular Diagnostic Testing of COVID-19.

With the rapid spread of the coronavirus disease (COVID-19), the need for rapid testing and diagnosis and consequently, the demand for mobile laboratories have increased. Despite this need, there are no clear guidelines for the operation, maintenance, or quality control of mobile laboratories. We provide guidelines for the operation, management, and quality control of mobile laboratories, and specifically for the implementation and execution of COVID-19 molecular diagnostic testing. These practical guidelines are primarily based on expert opinions and a laboratory accreditation inspection checklist. The scope of these guidelines includes the facility, preoperative evaluation, PCR testing, internal and external quality control, sample handling, reporting, laboratory personnel, biosafety level, and laboratory safety management. These guidelines are useful for the maintenance and operation of mobile laboratories not only in normal circumstances but also during public health crises and emergencies.

Update of Guidelines for Laboratory Diagnosis of COVID-19 in Korea.

Korean Society for Laboratory Medicine and the Korea Disease Prevention and Control Agency have announced guidelines for diagnosing coronavirus disease (COVID-19) in clinical laboratories in Korea. With the ongoing pandemic, we propose an update of the previous guidelines based on new scientific data. This update includes recommendations for tests that were not included in the previous guidelines, including the rapid molecular test, antigen test, antibody test, and self-collected specimens, and a revision of the previous recommendations. This update will aid clinical laboratories in performing laboratory tests for diagnosing COVID-19.

Early Laboratory Preparedness of the Korea Disease Control and Prevention Agency and Response to Unknown Pneumonia Outbreak from Wuhan, China, in January 2020.

We report the response process of the Laboratory Analysis Task Force (LATF) for Unknown Disease Outbreaks (UDOs) at the Korea Disease Control and Prevention Agency (KDCA) during January 2020 to coronavirus disease 2019 (COVID-19), which developed as a UDO in Korea. The advanced preparedness offered by the laboratory diagnostic algorithm for UDOs related to respiratory syndromes was critical for the rapid identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and enabled us to establish and expand the diagnostic capacity for COVID-19 on a national scale in a timely manner.

Estimating the origin and evolution characteristics for Korean HIV type 1 subtype B using Bayesian phylogenetic analysis.

The majority of Korean human immunodeficiency virus type 1 (HIV-1) isolates are composed of the Korean clade B strain that is distinct from the subtype B prevalent in North America and Europe. However, it is still not clear how HIV-1 was introduced, transmitted, and evolved within the Korean population. To identify the evolutionary characteristics of Korean HIV-1, we estimate the molecular epidemic history of HIV-1 subtype B gp120 env in Korea in comparison with sequences isolated from other geographic locations. A Bayesian Markov chain Monte Carlo (MCMC) statistical inference was used to estimate the time of divergence of subtype B. The estimated time of divergence of subtype B and the distinct monophyletic Korean B cluster was estimated to be in the early and mid-1960s, respectively. Substitution rates were estimated at 7.3×10(-3) and 8.0×10(-3) substitutions per site per year for HIV-1 subtype B and Korean clade B, respectively. The demographic dynamics of two Korean data sets showed that the effective number of infections in Korea increased rapidly until the early 1980s, and then the rate only slowly increased until the mid-1990s when the population growth approached a steady-state. These results suggest that the growth rate of prevalent HIV-1 strains in Korea was lower than in other countries, suggesting that the evolution of HIV-1 Korean clade B was relatively slow. Furthermore, the limited transmission of HIV-1 within the Korean population likely led to the independent evolution of this virus to form the HIV-1 Korean clade B.

Broad neutralizing antibody response and genetic variation in HIV-1 env genes in Koreans with primary HIV-1 infections.

To determine the neutralization profiles induced by HIV-1 Korean clade B, which has a monophyletic lineage and relative limited genetic diversity, we investigated the ability of HIV variants to elicit neutralizing antibodies in the immune response to primary infection. We selected seven Korean drug-naïve subjects with an HIV-1 primary infection and did pseudovirion-based neutralization assays using env genes of Korean HIV origin. The neutralizing antibody responses to the Korean clade B showed broad reactivity to subtype B but a highly subtype-specific pattern. The lengths of the amino acid sequences and the PNGS numbers in the V1-V5 region were positively correlated with neutralization. These results imply that the genetic characteristics of HIV-1 env may affect neutralizing antibody responses in HIV-1-infected individuals. This is the first report describing the relationship between neutralizing antibody responses and HIV-1 genetic characteristics in Korean subjects. It can be useful for developing AIDS vaccines against HIV-1 subtype B strains.

Neutralizing Antibody Responses and Evolution of the Viral Envelope in the Course of HIV-1 Korean Clade B Infection.

OBJECTIVES: HIV is able to continuously adapt to and evade the evolving neutralizing antibody responses of the host. We investigated the ability of HIV variants to evade neutralizing antibodies in order to understand the distinct characteristics of HIV-1 Korean clade B. METHODS: Three drug-naive subjects were enrolled in this study who were infected with HIV-1 Korean clade B. Neutralizations were performed using autologous plasma and pseudovirion-based assays in order to analyze and compare changes in the env gene. RESULTS: In the early phase of infection, neutralizing activities against autologous virus variants gradually increased, which was followed by a decline in the humoral immune response against the subsequent viral escape variants. The amino acids lengths and number of potential N-linked glycosylation sites (PNGS) in HIV-1 env gene was positively correlated with neutralized antibody responses during the early stages of infection. CONCLUSION: This study suggests that change within the env domains over the course of infection influences reactivities to neutralized antibodies and may also have an impact on host immune responses. This is the first longitudinal study of HIV-1 humoral immunity that took place over the entire course of HIV-1 Korean clade B infection.

Dynamic correlation between CTL response and viral load in primary human immunodeficiency virus-1 infected Koreans.

BACKGROUND: HIV-1 specific cytotoxic T lymphocytes (CTLs) have an important role as antiviral effector cells for controlling HIV-1 infection. METHODS: To investigate CTL response during the early stage of HIV infection, we measured immunity-related factors including CD4+ T cell counts, CD8+ T cell counts, HIV-1 RNA viral loads and IFN-γ secretion according to CTL response in 78 selected primary HIV-1-infected Koreans. RESULTS: The CTL response was strongly induced by HIV-1 specific Gag and Nef peptides (p = 0.016) compared with induction by Tat or Env peptides. These results suggest that the major antiviral factors inducing strong HIV-specific CTL responses are associated with the Gag and Nef viral regions in primary HIV-1 infected Koreans. The relationship between viral load and CTL response showed varying correlations with time following HIV infection. CTL response was inversely correlated with viral loads at preseroconversion stage I (r = -0.224 to -0.33) and changed to a positive correlation at the preseroconversion stage II (r = 0.132 to 0.854). Finally, it changed to an inverse correlation again after seroconversion until a viral set point was established on serological profiling (r = -0.195 to -0.407). CONCLUSIONS: These findings demonstrate a dynamic correlation between viral load and subsequent CTL responses during early HIV infection.

Increasing late diagnosis in HIV infection in South Korea: 2000-2007.

BACKGROUND: The number of Koreans diagnosed with human immunodeficiency virus (HIV) infections is increasing annually; however, CD4+ T-cell counts at diagnosis have decreased. The purpose of the present study was to identify clinical and epidemiologic associations with low CD4+ T-cell counts at the time of HIV diagnosis in a Korean population. METHODS: Data from 2,299 HIV-infected individuals with initial CD4+ T-cell counts measured within 6 months of HIV diagnosis and reason for HIV testing were recorded and measured from 2000 to 2007. Data were selected from the database of the Korea Centers for Disease Control and Prevention. Late diagnosis was defined by CD4+ T-cell counts <200 cells/mm3. Reasons for HIV testing were analyzed using logistic regression including epidemiologic variables. RESULTS: A total of 858 individuals (37.3%) were included in the late diagnosis group. Individuals with a late diagnosis were older, exposed through heterosexual contact, and demonstrated clinical manifestations of acquired immunodeficiency syndrome (AIDS). The primary reason for HIV testing was a routine health check-up (41%) followed by clinical manifestations (31%) of AIDS. The proportion of individuals with a late diagnosis was higher in individuals tested due to clinical symptoms in public health centers (adjusted odds ratio [AOR], 17.3; 95% CI, 1.7-175) and hospitals (AOR, 4.9; 95% CI, 3.4-7.2) compared to general health check-up. Late diagnosis annually increased in individuals diagnosed by voluntary testing both in public health centers (PHCs, P = 0.017) and in hospitals (P = 0.063). Routine testing due to risky behaviors resulted in earlier detection than testing secondary to health check-ups, although this difference was not statistically significant (AOR, 0.7; P = 0.187). Individuals identified as part of hospital health check-ups more frequently had a late diagnosis (P = 0.001) CONCLUSIONS: HIV infection was primarily detected by voluntary testing with identification in PHCs and by testing due to clinical symptoms in hospitals. However, early detection was not influenced by either voluntary testing or general health check-up. It is important to encourage voluntary testing for early detection to decrease the prevalence of HIV infection and AIDS progression.

Antiretroviral genotypic resistance mutations in HIV-1 infected Korean patients with virologic failure.

Resistance assays are useful in guiding decisions for patients experiencing virologic failure (VF) during highly-active antiretroviral therapy (HAART). We investigated antiretroviral resistance mutations in 41 Korean human immunodeficiency virus type 1 (HIV-1) infected patients with VF and observed immunologic/virologic response 6 months after HAART regimen change. Mean HAART duration prior to resistance assay was 45.3+/-27.5 months and commonly prescribed HAART regimens were zidovudine/lamivudine/nelfinavir (22.0%) and zidovudine/lamivudine/efavirenz (19.5%). Forty patients (97.6%) revealed intermediate to high-level resistance to equal or more than 2 antiretroviral drugs among prescribed HAART regimen. M184V/I mutation was observed in 36 patients (87.7%) followed by T215Y/F (41.5%) and M46I/L (34%). Six months after resistance assay and HAART regimen change, median CD4+ T cell count increased from 168 cells/microL (interquartile range [IQR], 62-253) to 276 cells/microL (IQR, 153-381) and log viral load decreased from 4.65 copies/mL (IQR, 4.18-5.00) to 1.91 copies/mL (IQR, 1.10-3.60) (P<0.001 for both values). The number of patients who accomplished viral load <400 copies/mL was 26 (63.4%) at 6 months follow-up. In conclusion, many Korean HIV-1 infected patients with VF are harboring strains with multiple resistance mutations and immunologic/virologic parameters are improved significantly after genotypic resistance assay and HAART regimen change.

National survey of prevalent HIV strains: limited genetic variation of Korean HIV-1 clade B within the population of Korean men who have sex with men.

The evolution of HIV is the result of an explosive combination of factors-a high rate of mutation, replication dynamics, frequent recombination, and natural selection. To understand the evolution of the distinctive Korean HIV-1 B clade, we investigated the characteristics of the genetic variation of the HIV-1 subtype B env gene within the group of Korean men who have sex with men (MSM). From 1985 to 2005, 700 HIV-1-infected Koreans were sequenced at the V1 to V5 region of the HIV-1 env gene. In the phylogenetic analysis, 560 isolates were identified as HIV-1 subtype B, and 489 of the 560 isolates were HIV-1 Korean clade B. Based on epidemiologic investigation, 249 of 700 HIV-1-infected patients were HIV-1 subtype B-infected MSM. Interestingly, the proportion of the GPGS motif in MSM infected by Koreans was 1.6 times higher than in MSM infected by foreigners, and the genetic expansions of diversity and divergence for HIV-1 subtype B in Korean MSM were 2.1% and 2.5%, respectively. This was much lower than those observed in other countries. Therefore, our findings imply that the HIV strains in this group were closely related. This result may be helpful for understanding the evolution of the distinct HIV-1 Korean B clade.

Early identification of seronegative human immunodeficiency virus type 1 infection with severe presentation.

Specific antibodies against human immunodeficiency virus (HIV), usually used for diagnosis, almost invariably become detectable within 3 months of exposure. We report on a patient whose HIV infection was identified early by a combined antigen/antibody test, but seroconversion did not occur for 7 months, until the implementation of antiretroviral therapy.

Molecular investigation of human immunodeficiency virus type 2 subtype a cases in South Korea.

We investigated the molecular characteristics of human immunodeficiency virus type 2 (HIV-2) subtype A isolates to clarify the transmission mode of HIV-2 within Korea. These findings indicated that the viruses from the six patients infected within Korea formed a distinct subcluster in the phylogenetic tree and might have been transmitted from one source.